[Pathological changes in the nervous structures of the aortic wall tissue adjacent to an unstable atherosclerotic plaque]. / Patologicheskie izmeneniya nervnykh struktur v tkanyakh stenki aorty, prilezhashchikh k nestabil'noi ateroskleroticheskoi blyashke.

OBJECTIVE: To study of nerve structures in the aortic wall in atherosclerosis using a complex of immunohistochemical markers. MATERIAL AND METHODS: The objects of the study were excised fragments of the wall of the thoracic and abdominal aorta along with visually determined unstable atherosclerotic plaques. To study nerve structures on paraffin sections, immunohistochemical reactions were performed for the PGP 9.5 protein, tyrosine hydroxylase, and synaptophysin. RESULTS: It has been established that pronounced pathological changes are observed in the nervous structures of the aortic wall near unstable atherosclerotic plaques. Reactive, dystrophic, and severe degenerative changes in neurocytes, nerve fibers, and glial cells are described in the elements of the nervous apparatus of the adventitia (microganglia, nerve trunks, and nerve plexuses). It was found that only sympathetic neurons and their postganglionic fibers remain in the intramural ganglia, while the structures of the parasympathetic nervous apparatus undergo degeneration. Destruction of perivascular nerve plexuses and vasa vasorum in the adventitia, as well as degeneration of varicose axons of the main terminal synaptic plexus at the border of adventitia and superficial smooth muscle layer of the media were demonstrated. CONCLUSION: It is assumed that the presence of inflammatory infiltrates in the adventitia and intima, denervation and death of vasa vasorum can serve as factors determining the development of the atherosclerotic process.

[The role of neovascularization in the formation of an unstable human atherosclerotic plaque]. / Rol' neovaskulyarizatsii v formirovanii nestabil'noi ateroskleroticheskoi blyashki u cheloveka.

MATERIAL AND METHODS: The study material was 20 autopsy samples obtained from males aged 65 to 72 years who died from acute atherosclerotic cardiovascular insufficiency. Aortic segments (from the arch, thoracic and abdominal regions), coronary arteries and the arteries of the base of the brain (a. basilaris) were investigated; these totaled 45 tissue segments. Neovessels and cellular responses in the arterial wall were examined by hematoxylin and eosin staining. VEGF was immunohistochemically detected using a highly sensitive two-stage streptavidin-biotin method. RESULTS: In unstable atherosclerotic lesions, there were active neovascularization processes in both the fibrous cap and the underlying parts of the adventitia. These changes are usually combined with a pronounced cellular inflammatory response that can contribute to their development. Endothelial growth factor may be one of the causes of neovascularization in unstable atherosclerotic lesions. CONCLUSION: A comparative immunomorphological study in the human aorta, coronary arteries, and a. basilaris revealed active neovascularization processes in the cap and the underlying parts of the adventitia in unstable atherosclerotic lesions. The cause of this neovascularization is probably endothelial growth factor and cellular inflammatory responses.

[Macrophages and Their Role in Destabilization of an Atherosclerotic Plaque].

The modern data on structure and the functional activity of macrophages are presented in the review. It is shown that they are the nonhomogeneous cell population. Two of their main subpopulations are presented as M1 and M2 phenotypes which perform opposite functions at inflammation development. The main attention in the review is paid to a role of macrophages in pathogenesis of atherosclerosis and, first, in formation of unstable atherosclerotic plaques which are the cause of the most severe complications of the disease. It is shown that main subpopulations of macrophages play different roles in formation of unstable and stable atherosclerotic plaques. Macrophages of M1 phenotype in the vascular wall carry out pro-atherogenic role and influence destabilization of an atherosclerotic plaque, while M2 macrophages perform atheroprotective function.

[To the 130th anniversary since the birth of the prominent pathologist N.N. Anichkov, academician of USSR Academy of sciences and Academy of medical sciences].

The paper represents the research achievements and a course of life of the outstanding Russian pathologist, founder of the doctrine on atherosclerosis academician Nikolai Nikolayevich Anichkov.

Myocardial tissue damage in rabbits injected with group A streptococci, types M1 and M22. Role of bacterial immunoglobulin G-binding surface proteins.

Acute rheumatic fever (ARF) and acute poststreptococcal glomerulonephritis (APSGN), two important sequelae of streptococcal throat or skin infections, according to current concepts may be elicited by autoimmune mechanisms due to molecular mimicry between group A streptococci (GAS) and human tissue. In the case of APSGN, however, our experimental data have indicated that GAS immunoglobulin-binding surface proteins (IgG BPs) might be of pathogenic significance by triggering anti-IgG production and immune complex formation leading to renal damage. Thus, rabbits injected with IgG-binding, as opposed to non-binding, GAS strains were found to develop renal deposition of IgG and complement factor C3 and inflammatory and degenerative glomerular changes resembling the picture seen in APSGN. In the present study, cardiac tissue material from rabbits injected with GAS was investigated. After 8 or more weeks of intravenous (i.v.) injections, minimal changes were seen in those animals receiving an IgG non-binding GAS strain, type T27, whereas those animals receiving either of two IgG-binding GAS strains, types M1 or M22, developed strong inflammatory and degenerative myocardial changes accompanied by deposition of IgG and C3. Furthermore, on injecting rabbits with defined mutants of a type M22 strain, the development of myocardial tissue damage proved to be dependent on the presence of streptococcal IgG-binding activity. Our results demonstrate that myocardial tissue changes may be induced in the rabbit by i.v. injection of whole heat-killed GAS of at least two M serotypes. Conceivably, induction of immune complexes by bacterial IgG BPs may lead to myocardial deposition of IgG, in turn triggering a series of events, involving the complement system and proinflammatory cytokines, with resulting tissue damage. Though many virulence factors may be involved in the development of ARF and APSGN, and a given GAS strain will never cause both, our results may suggest a new pathogenetic mechanism common to these two major non-suppurative complications.

Induction of myocarditis in rabbits injected with group A streptococci.

BACKGROUND & OBJECTIVES: We have earlier proposed that group A streptococcal (GAS) immunoglobulin binding surface proteins (IgGBPs) might trigger anti-IgG production and immune complex formation leading to glomerulonephritis. In the present study, cardiac tissue material from rabbits injected with heat-killed GAS was investigated. METHODS: Rabbits were injected intravenously with 10(9) colony forming units of streptococci three times weekly for 8 wk. Cardiac tissue samples were obtained at different times and deposition of IgG, C3, TNF-alpha and IL-6 was studied. RESULTS: After 8 or more weeks of intravenous (iv) injections, minimal changes were seen in animals receiving an IgG non-binding GAS strain, type T27, whereas in those animals receiving either of two IgG binding GAS strains, types M1 or M22, strong inflammatory and degenerative myocardial changes accompanied by deposition of IgG and C3 were noted. Furthermore, on injecting rabbits with defined mutants of a type M22 strain, the development of myocardial tissue damage proved to be dependent on the presence streptococcal IgGBPs. INTERPRETATION & CONCLUSION: The present data supported a role of streptococcal IgGBPs in the induction of myocardial tissue injury by GAS.

Triggering of renal tissue damage in the rabbit by IgG Fc-receptor-positive group A streptococci.

Our previous studies have shown that streptococcal IgG Fc receptors (FcR) act to elicit circulating anti-IgG as well as renal glomerular deposition of IgG in rabbits immunized with group A streptococci (GAS). In order to study if other FcR-positive bacteria might have similar effects, rabbits were immunized with either group G streptococci (GGS; strain G148) or Staphylococcus aureus (strain Cowan I) for two periods of 8 and 6 weeks, respectively. At the end of immunization, circulating anti-IgG was found in 6 of 20 (30%) and 4 of 19 (21%) animals receiving G148 and Cowan I, respectively, compared to all 28 receiving FcR-positive GAS strains of types M1, M4, M15 or M22 (p < 0.05 for both comparisons); furthermore, anti-IgG appeared earlier and at higher levels in the GAS groups. Weak glomerular IgG deposits occurred in 5 out of 10 (50%) and 2 out of 8 (25%) animals immunized with G148 and Cowan I, respectively. In contrast, all 11 rabbits examined, given GAS of types M1 or M15, displayed heavy deposits. None of four control animals immunized with either of two FcR-negative strains, GAS type T27 or group B streptococci (GBS) type Ia, exhibited any renal IgG deposits or circulating anti-IgG. Renal tissue materials from rabbits immunized with any of the four FcR-positive GAS strains showed strong inflammatory and degenerative glomerular changes, compatible with the picture seen in acute poststreptococcal glomerulonephritis (APSGN). Only transient renal changes were found in those rabbits immunized with G148 or Cowan I, or the controls injected with the FcR-negative strains, GAS type T27 or GBS. Thus, only the FcR-positive GAS strains showed capacity to induce high levels of anti-IgG, pronounced tissue deposition of IgG as well as irreversible glomerular changes. Our experimental data suggest that streptococcal IgG FcR activity might play an important role in triggering APSGN.